Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman’s syndrome
| Autor: | Zhao Guangfeng, Yali Hu, Xiaoqiu Tang, Hui Zhu, Yun Cao, Yan Zhou, Jianwu Dai, Jingjie Lu, Chenyan Dai, Tong Ru, Xianghong Zhu, Lijun Ding, Haixiang Sun, Guijun Yan, Xin’an Li, Ruotian Li, Juan Li, Bin Wang, Caimei Lin, Yimin Dai, Lei Wang, Jingmei Wang, Huiyan Wang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Transplantation Down-Regulation Bone Marrow Cells Asherman's syndrome Gynatresia Biology Real-Time Polymerase Chain Reaction Endometrium Peripheral blood mononuclear cell General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Downregulation and upregulation Environmental Science(all) medicine Humans Pathological General Environmental Science Agricultural and Biological Sciences(all) Tissue Scaffolds Biochemistry Genetics and Molecular Biology(all) Tumor Suppressor Proteins Regeneration (biology) medicine.disease Transplantation 030104 developmental biology medicine.anatomical_structure Immunology Cancer research Female Collagen General Agricultural and Biological Sciences Collagen scaffold Transcription Factors |
| Zdroj: | Science China Life Sciences. 60:404-416 |
| ISSN: | 1869-1889 1674-7305 |
| DOI: | 10.1007/s11427-016-0328-y |
| Popis: | Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS. |
| Databáze: | OpenAIRE |
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